Title: The Association of the 4q25 Susceptibility Variant for Atrial Fibrillation With Stroke Is Limited to Stroke of Cardioembolic Etiology
Authors: Lemmens, Robin ×
Buysschaert, Ian
Geelen, Veerle
Fernandez, Israel
Montaner, Joan
Schmidt, Helena
Schmidt, Reinhold
Attia, John
Maguire, Jane
Levi, Christopher
Jood, Katarina
Blomstrand, Christian
Jern, Christina
Wnuk, Marcin
Slowik, Agniezska
Lambrechts, Diether
Thijs, Vincent #
Issue Date: Sep-2010
Publisher: Lippincott Williams & Wilkins
Series Title: Stroke vol:41 issue:9 pages:1850-1857
Abstract: BACKGROUND AND PURPOSE: Genome-wide association studies recently identified 2 variants on chromosome 4q25 as susceptibility factors for atrial fibrillation. Interestingly, these variants were subsequently also shown to be associated with stroke. However, it remains unclear whether 4q25 associates with all the stroke subtypes or with cardioembolic stroke in particular, which is often attributable to atrial fibrillation. METHODS: We performed a large case-control association study in 4199 ischemic stroke patients, all subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria, and 3750 controls derived from 6 studies conducted in Australia, Austria, Belgium, Poland, Spain, and Sweden. Two variants on chromosome 4q25, rs1906591 and rs10033464, were genotyped. RESULTS: Within cases, the A-allele of rs1906591 was associated with atrial fibrillation (odds ratio, 1.64 [95% CI, 1.43 to 1.90]; P=9.2 . 10(-12)), whereas rs10033464 was only marginally associated. There was an association between overall ischemic stroke and rs1906591 (odds ratio, 1.20 [95% CI, 1.09 to 1.32]; P=1.2 . 10(-4)). However, this was probably caused by the large effect of stroke of cardioembolic etiology because no relation was obtained in any other subgroup of stroke. The rs10033464 variant failed to show any relationship with ischemic stroke. CONCLUSIONS: We replicated the association of the rs1906591 variant on chromosome 4q25 with atrial fibrillation and ischemic stroke of cardioembolic etiology. The 4q25 locus failed to associate with noncardiac subtypes of ischemic stroke.
ISSN: 0039-2499
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Vesalius Research Centre (-)
Laboratory for Neurobiology (Vesalius Research Center)
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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